Dermis is a skin layer between epidermis and hypodermis, the layer containing fibroblasts that are involved in producing components of dermis. Up to 85% of dermis consists of collage. A variety of intrinsic and extrinsic factors may affect production of components of dermis and especially collagen, thus, leading to undesirable outward visible and tactilely perceptible changes in skin. For example, chronological aging is accompanied with loss of components of dermis and development of discontinuities in dermis structure that contributes to wrinkles and lines formation, loss of skin elasticity and firmness. Another factor is a mechanical tension of skin of subjects that is frequently observed, e.g. under pregnancy, during growth spurts, and gain weight. This tension factor may lead to development of tears in the dermis known as stretch marks. Excessive regional fat under cellulite may induce weakening dermis structure, fat protrusions into lower dermis, and uneven distribution of subcutaneous tissue giving rise to outward visibly and tactilely perceptible an irregular, dimpled skin surface also known as “orange peel”. Thus, there is a great need in safe and effective agents for the improvement of dermis components production reducing dermis discontinuities under abovementioned unfavorable conditions.
Interleukin-1 alpha, which is also named IL-1F1, is a naturally occurring polypeptide with the sequence well-known from the art. Interleukin-1 alpha is synthesized as 31-kDa precursor, and is secreted by cells in active form of about 18-kDa. Interleukin-1 alpha is the only interleukin-1 family member that is constitutively produced in active form by human epidermis in norm. Healthy human skin contains interleukin-1 alpha in levels of about 10 to 13 ng/g, which levels are frequently decreased, for example, in conditions of psoriatic or aging skin. Mizutani H, et al., J Clin Invest. 1991, 87(3):1066-71. Wood L C, et al., J Clin Invest 1992: 90: 482-487. Se Kyoo Jeong, et al., Exp. Dermatology 2005: 14: 571-579. Chantel O., et al., J Invest Dermatol 122:330-336, 2004. Nowinski D, et al, J Invest Dermatol. 2002; 119(2):449-55. Bonifati C, et al., J Biol Regul Homeost Agents. 1997, 11(4):133-6. Takematsu H, et al. Tohoku J Exp Med. 1990, 161(3):159-69.
The use of interleukin-1 alpha in medicinal applications is known from the art. For example, U.S. Pat. No. 4,816,436 discloses a process for treating arthritis or inflammation with the use of intra-articular, intramuscular, intravenous, or intraperitoneal injections of interleukin-1 alpha; U.S. Pat. No. 5,120,534 discloses a method for treating thrombocytopenia by administering interleukin-1 alpha or Asp36, Ser141-derivative of interleukin-1 alpha; U.S. Pat. No. 5,534,251 discloses stabilized medicinal composition comprising Asp36, Ser141-derivative of interleukin-1 alpha; EP0391444 discloses a pharmaceutical composition comprising interleukin-1 alpha, and suitable for forming a parenterally administratable aqueous formulation; WO9116916, JP4018033, EP0482213, and ES2121782T disclose an antitumor composition containing the combination of interleukin-1 and gamma-interferon.
Although interleukin-1 alpha stimulates dermal production of procollagen, the collagen precursor, by dermal fibroblasts, it also stimulates production of collagenase, the collagen destroying enzyme. Postlethwaite et al., J Cell Biol. 1988, 106(2):311-8. Duncan et al., J Invest Dermatol. 1989, 92(5):699-706. Thus, it is not known from the art, whether applying interleukin-1 alpha to the skin produces overall positive or negative effect on collagen content in skin and dermis density. No published or disclosed in the art related to cosmetic and dermatological methods for treating cellulite, stretch marks, or reducing signs of aging skin with topically applied interleukin-1 alpha.